A model has previously been reported which is characterized by a cyclical production of antibody following a single injection of aggregated human gamma globulin (AHGG) into rabbits. It is now proposed to study the cellular parameters involved in this cyclical phenomenon. Since preliminary experiments have indicated the events that initially occur in the spleen may regulate that response to HGG resulting from stimulation of distal lymph nodes, experiments have been designed to determine the role of the spleen and possibly putative splenic suppressor cells in the regulation of the response in other lymphoid tissue. Other studies will be carried out to determine the immune status of the lymphoid cells (both T and B cell) at various phases during both remission and activation of the immune response following stimulation with AHGG. In addition, the role of complement in the fate of persistent antigen and the ultimate effect of both complement and the persistence of antigen on the cycling phenomenon will be determined. Other studies will be directed at adaptation of the cyclical phenomenon to both synergistic and in vitro models. Attempts will be made, utilizing the vitro model, to study the effect of modulation of the Ig receptor and the antigen-receptor complex on regulation of the immune response.